Action of Specific Estrogens on Vascular Cells

Abstract

Coronary heart disease (CHD) is a major cause of mortality in First World countries in both men and women. Men exhibit up to a tenfold greater risk of CHD than women of premenopausal age. In women undergoing natural [1] or surgical menopause [2], the risk of CHD increases and approaches that of men. Cessation of ovarian function and loss of endogenous sex hormone production has been suggested to be the primary cause of the increase in risk of CHD observed in postmenopausal women. Indeed, hormone replacement therapy (HRT) studies have indicated that hormone replacement is associated with a reduction in both morbidity and mortality of around 50% [3]. This discrepancy in risk of CHD between the genders has prompted intense research into the vascular effects of female sex hormones. Studies on coronary occlusion as assessed by selective coronary arteriography have revealed that HRT users had a relative risk of coronary artery disease of 0.37–0.44 compared to non-users [4]. The female sex hormones, in particular estrogen, are believed to cause their relative cardioprotection in part by alterations in plasma lipoprotein levels [5]. Estrogens are able to increase plasma high density lipoproteins (HDL) while lowering low density lipoproteins (LDL) [6]. Given the positive association of the latter with CHD risk and the association of the former with cardiovascular protection, it was at first believed that this was the primary mechanism by which female sex hormones mediated cardiovascular benefit. However, studies quantifying the relative contribution of these changes to cardioprotection, concluded that changes in lipid profiles at most accounted for only 25%–50% of the effect of female sex hormones [7].